Gold catalysis cyclization

Tertiary N-butynylamine 48 when oxidized generates an N-oxide intermediate that is cyclized in situ via gold catalysis to give bicyclic piperidone 49 (09JA8394). As amine 48 can be prepared readily, the overall transformation constitutes a formal [4+2] synthesis. 

The Conia-ene reaction was brought to the held of gold catalysis by Toste et al.29 It provided very mild conditions for this cyclization to a functionalized hve-membered ring (Scheme 12.14). 

The cycloisomerization of a-allenyl ketones to the corresponding substituted furans was the first example of a gold-catalyzed addition of an oxygen nucleophile to an allene (Scheme 4-86). Traditionally, silver or palladium catalysts were employed for cyclizations of this type advantages of gold catalysis incluiie shorter reaction times, milder conditions, an or lower catalyst loadings. Variable amounts of... 

Two types of carbon nucleophiles are commonly utilized in gold catalysis electron-rich (hetero)arenes [3,6] and 1,3-carbonyl compounds [94—104]. The first will be discussed later. The addition of 1,3-carbonyl compounds to alkynes, known as the Conia-ene cyclization [94—104], takes place via the corresponding enol tautomer or the corresponding silyl enol ether (Scheme 1.4). 

A variety of other cyclization reactions are also observed with many of the carbon cumulenes. Especially, allenes and ketenes undergo many of these reactions and gold catalysis has achieved a new dimension in selectivity. From bis-allenes, complex natural products, such as 18,19 norsteroids, are generated in one step. 

The compound (2-ethynylphenyl)methanol 88 (X = O) and the corresponding phenylmethanamine 89 (X = NTs) were also used by the group of Xu in 2013 [45] for the preparation of spiroacetals 90 (X = O) and spiroaminals 91 (X = NTs), respectively (Scheme 9.25). This bimetallic relay catalysis sequence includes a gold-mediated cyclization followed by a Lewis acid-catalyzed inverse-electron-... 

Harkat H, Blanc A, Weibel J-M, Pale P (2008) Versatile and expeditious synthesis of aurones via Au -catalyzed cyclization. J Org Chem 73(4) 1620-1623. doi 10.1021/jo702197b Hashmi ASK, Schuster AM, Rominger F (2009) Gold catalysis isolation of vinylgold complexes derived from alkynes. Angew Chem, Ind Ed 48 8247-8249. doi 10.1002/anie.200903134 Heine HW, Henzel RP (1969) Aziridines. XXL l,4-Diazabicyclo[4.1.0]hept-4-enes and 1,1a-dihydro-l,2-diarylazirino[l,2-a]quinoxalines. J Org Chem 34(1) 171-174. doi 10.1021/ jo00838a037... 

In 2010, Gouverneur and coworkers reported a novel cascade cyclization-intermolecular alkynylation reactions toward the synthesis of five-membered 0-heterocycles. /i-Alkynyl-y-butenolides 2 could be efficiently prepared from allenoates 1 and terminal alkynes in the presence of a gold catalyst with the use of Selectfluor as an external oxidant (Scheme 12.1) [5]. This process involves a direct C(sp)-H functionalization of terminal alkynes. This novel gold-catalyzed cascade cyclization oxidative cross-coupling process provides a basis for the development of novel cascade reactions combining traditional gold catalysis and intermolecular oxidative alkynylation. 

Using a similar dual gold catalysis of diynes model, Hashmi, Hansmann, and coworkers explored a dual gold-catalyzed cyclization of 3,4-diethynylthiophenes to generate pentaleno[c]thiophenes through gold-vinylidenes and C-H bond activation. In these cases, 5-e (io-dig cyclization pathway was observed. This protocol can be used to construct thiophene/furan or thiophene/pyrrole 101 system skeleton from 3,4-diethynylthiophene derivatives 100 (Scheme 12.46) [49]. 

A gold catalysis-initiated cascade process toward the synthesis of electron-rich arene-fused hexahydroquinolizinones 131 was developed by Zhang and Liu in 2012 (Scheme 12.57) [62]. In this cascade reaction, a gold-catalyzed amide cyclization to a tethered C-C triple bond initiates a subsequent Frie del-Crafts type cyclization, followed by a Ferrier rearrangement. Synthetic utility of this... 

By combining an initial gold-catalyzed hydroaminative indole formation with repetitive hydroarylations, Hirano et al. [48] reported the gold-catalyzed direct construction of highly fused carbazoles by multiple cyclization. Scheme 4.28 shows one example of this chemistry, and the overall yield of this pentacyclization is excellent, highlighting the efficiency of gold catalysis. 

Sames et al. studied the cyclization of phenyl/propargyl ethers catalyzed by different metal salts since this Friedel-Crafts alkenylation had previously been reported to be catalyzed by metals such as Pd, Zr In and Sc [122-124] or even zeolites by hereogeneous catalysis [125]. In this preliminary research, the maximum yield of the desired product achieved by gold was only 6%, the best results being obtained with PtCl2 as catalyst [126]. 

However, the ability of gold(III) chloride to provide protic catalysis under exceptionally mild conditions is further demonstated by two recent examples the hydroxyallene 35 bearing a silyl protecting group is efficiently cyclyzed to give the 2,5-dihydrofuran 36 without deprotection [20] other acidic catalysts which in principle sufficiently promote this type of cyclization - such as HC1 gas or Amberlyst 15 resin - are of course much less compatible with acid sensitive functionalities. Also for the formation of macrocycle 39 gold(III) chloride turned out to be the catalyst of choice [21],... 

Dake s group84 published an interesting report in which AgOTf and cationic gold (I) complexes were compared for their use in the synthesis of the pyrrole scaffold. From (3-alkynyl ketones 66 (Scheme 5.29) and various primary amines 67, the imine intermediates JJ were formed in situ and the intramolecular cyclization produced various pyrroles 68. Both catalysts AgOTf (5 mol%) or Au(PPh3)OTf (5 mol%) were efficient, but the reaction proceeded more rapidly with silver catalysis. 

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